Ignite Creation Date:
2024-05-06 @ 5:10 PM
Last Modification Date:
2024-10-26 @ 2:23 PM
Study NCT ID:
NCT05215808
Status:
RECRUITING
Last Update Posted:
2023-10-23
First Post:
2022-01-18
Brief Title:
SADMAD Safety and PK Study of RBN-3143 in Healthy and Atopic Dermatitis Subjects
Sponsor:
Ribon Therapeutics Inc
Organization:
Ribon Therapeutics Inc
Study Overview
Official Title:
A First-in-Human Randomized Placebo-Controlled Phase 1 Single and Multiple Ascending Dose Study to Assess the Safety and Pharmacokinetics of RBN-3143 in Healthy Subjects and as Open-Label in Patients With Atopic Dermatitis Subjects
Status:
RECRUITING
Status Verified Date:
2023-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
RBN-3143 Background PARP proteins are members of a family of seventeen ADP-ribosyltransferase ART enzymes that regulate cellular processes including gene expression protein degradation and multiple cellular stress responses RBN-3143 is a PARP-14 inhibitor PARP14 is over-expressed in tissues with inflammatory diseases RBN-3143 is a novel orally administered PARP14 inhibitor that was developed to be evaluated as therapy for a range of inflammatory diseases with an initial focus on Atopic Dermatitis
Study Overview The study consists of 2 parts Part A This part of the study is being conducted in a clinical research unit CRU and is enrolling healthy adult subjects to determine the safety of RBN-3143 its absorption metabolism and excretion what the body does to this drug and will assess its potential pharmacodynamic properties what the drug does to the body
There are 3 subsections to this part of the study The first segment was conducted in a double-blind manner neither the investigator nor subject knew if placebo or RBN-3143 was given to assess dosing regimens of RBN-3143 when taken in a fasted state before food The last two segments are currently recruiting and are Open Label all subjects will receive RBN-3143 and will assess RBN-3143 when taken with food with pantoprazole a medication that decreases the amount of acid in the stomach and with midazolam
Part B In early 2023 the second part of the study will be conducted in patients with moderate to severe atopic dermatitis to measure the pharmacodynamic activity of RBN-3143 and evaluate preliminary efficacy of 28 days administration of the study drug All patients will receive the same dose of RBN-3143
Study Overview The study consists of 2 parts Part A This part of the study is being conducted in a clinical research unit CRU and is enrolling healthy adult subjects to determine the safety of RBN-3143 its absorption metabolism and excretion what the body does to this drug and will assess its potential pharmacodynamic properties what the drug does to the body
There are 3 subsections to this part of the study The first segment was conducted in a double-blind manner neither the investigator nor subject knew if placebo or RBN-3143 was given to assess dosing regimens of RBN-3143 when taken in a fasted state before food The last two segments are currently recruiting and are Open Label all subjects will receive RBN-3143 and will assess RBN-3143 when taken with food with pantoprazole a medication that decreases the amount of acid in the stomach and with midazolam
Part B In early 2023 the second part of the study will be conducted in patients with moderate to severe atopic dermatitis to measure the pharmacodynamic activity of RBN-3143 and evaluate preliminary efficacy of 28 days administration of the study drug All patients will receive the same dose of RBN-3143
Detailed Description:
The study consists of 2 parts
Part A This part of the study is being conducted in a clinical research unit CRU and will enroll healthy adult subjects to determine the safety of RBN-3143 its absorption metabolism and excretion what the body does to this drug and will assess its potential pharmacodynamic properties what the drug does to the body
There are 3 subsections to this part of the study The first subsection has completed enrollment and the 2 open-label subsections are now actively enrolling
1 Double-Blind Cohorts- Fasting In the first segment of the study subjects were randomized in a double-blind manner using a 31 ratio RBN-3143 placebo to receive either RBN-3143 or placebo Subjects were enrolled in groups of ascending doses
2 Open Label Cohorts
1 Food EffectProton Pump Inhibitor FEPPI Open Label Cohort
Twelve 12 additional subjects are being enrolled and will receive RBN-3143 with food fed fasted or with pantoprazole PPI a drug to determine if the amount of acid in the stomach as well as the presence or absence of food changes how RBN-3143 is absorbed Subjects will be required to stay in the CRU for up to 16 days Two sequences will be studied either fasted then fed or fed then fasted with both sequences followed by administration of a proton pump inhibitor
2 Drug-Drug Interaction DDI Open Label Cohort A further 12 subjects are being enrolled into a DDI cohort to evaluate the effect of RBN-3143 on the exposure of midazolam a sensitive CYP3A4 substrate Subjects will be required to stay in the CRU 19 days Subjects will also return for a final visit approximately 1 week later This cohort will have 2 Treatment Periods as follows
Treatment Period 1 On Day 1 subjects will be administered a single oral dose of 2 mg midazolam in the fasted state
Treatment Period 2 Subjects will be administered RBN-3143 in the fasted state from Day 3 through Day 17 14- day treatment period On Day 16 subjects will also receive a single oral dose of 2 mg midazolam in the fasted state
Part B In early 2023 the second part of the study will be initiated in approximately 12 patients with moderate to severe atopic dermatitis All patients will receive the same doses of RBN-3143 for 28 days
On Day 1 and Day 28 patients will fast overnight until after the morning dose administration then fast for 4 hours post-dose On all other days fasted state will be 2 hours prior to dosing and 2 hours after dosing Patients will be required to present at the CRU on Day -1 for required study assessments after which they may return home Patients will return to the CRU on Day 1 for the day 1 dose and the completion of required study assessments Patients will then return home with sufficient study drug to complete dosing on Days 2 to Day 27 inclusive Patients will be required to attend the CRU for completion of required assessments on Day 7 Day 14 Day 21 and Day 28 and will return any remaining study drug on the Day 28 visit Patients will return for an EOSFollow-up visit at 4 weeks after the last dose of study drug
Collection of data will cease at the time of database lock for final safety and PK analysis
Part A This part of the study is being conducted in a clinical research unit CRU and will enroll healthy adult subjects to determine the safety of RBN-3143 its absorption metabolism and excretion what the body does to this drug and will assess its potential pharmacodynamic properties what the drug does to the body
There are 3 subsections to this part of the study The first subsection has completed enrollment and the 2 open-label subsections are now actively enrolling
1 Double-Blind Cohorts- Fasting In the first segment of the study subjects were randomized in a double-blind manner using a 31 ratio RBN-3143 placebo to receive either RBN-3143 or placebo Subjects were enrolled in groups of ascending doses
2 Open Label Cohorts
1 Food EffectProton Pump Inhibitor FEPPI Open Label Cohort
Twelve 12 additional subjects are being enrolled and will receive RBN-3143 with food fed fasted or with pantoprazole PPI a drug to determine if the amount of acid in the stomach as well as the presence or absence of food changes how RBN-3143 is absorbed Subjects will be required to stay in the CRU for up to 16 days Two sequences will be studied either fasted then fed or fed then fasted with both sequences followed by administration of a proton pump inhibitor
2 Drug-Drug Interaction DDI Open Label Cohort A further 12 subjects are being enrolled into a DDI cohort to evaluate the effect of RBN-3143 on the exposure of midazolam a sensitive CYP3A4 substrate Subjects will be required to stay in the CRU 19 days Subjects will also return for a final visit approximately 1 week later This cohort will have 2 Treatment Periods as follows
Treatment Period 1 On Day 1 subjects will be administered a single oral dose of 2 mg midazolam in the fasted state
Treatment Period 2 Subjects will be administered RBN-3143 in the fasted state from Day 3 through Day 17 14- day treatment period On Day 16 subjects will also receive a single oral dose of 2 mg midazolam in the fasted state
Part B In early 2023 the second part of the study will be initiated in approximately 12 patients with moderate to severe atopic dermatitis All patients will receive the same doses of RBN-3143 for 28 days
On Day 1 and Day 28 patients will fast overnight until after the morning dose administration then fast for 4 hours post-dose On all other days fasted state will be 2 hours prior to dosing and 2 hours after dosing Patients will be required to present at the CRU on Day -1 for required study assessments after which they may return home Patients will return to the CRU on Day 1 for the day 1 dose and the completion of required study assessments Patients will then return home with sufficient study drug to complete dosing on Days 2 to Day 27 inclusive Patients will be required to attend the CRU for completion of required assessments on Day 7 Day 14 Day 21 and Day 28 and will return any remaining study drug on the Day 28 visit Patients will return for an EOSFollow-up visit at 4 weeks after the last dose of study drug
Collection of data will cease at the time of database lock for final safety and PK analysis
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None